Development of a Mathematical Model for Predicting Accurate Hepatic Clearance of Drug

Clearance (CL), the amounts of a drug metabolized by enzymes per unit time, is the major pharmacokinetic measurement used in the development and determination of the dosage of medications. In vivo hepatic CL of a drug has been predicted by extrapolating in vitro intrinsic CL whose estimation is based on the Michaelis-Menten (MM) equation, which is the result of the standard quasi-steady-state approximation (QSSA). However, in vivo drug CL predicted in that way becomes inaccurate if in vivo hepatic enzyme concentration is not sufficiently lower than the MM constant of the drug. Here, we develop an alternative approach based on the total QSSA, which accurately predicts in vivo CL of drugs regardless of their MM constant values.